tbuckley/cabot-search huggingface dataset:
Quality of life (QoL) in patients with recurrent ovarian clear cell carcinoma (rOCCC) receiving durvalumab (D) versus physician’s choice chemotherapy (PCC) in the randomized phase II MOCCA/APGOT-OV2/GCGS-OV3 trial.
Authors: Natalie YL Ngoi, Haoyang Sun, Chel Hun Choi, Valerie Heong, Samuel Guan Wei Ow, Wen Yee Chay, Hee Seung Kim, Geraldine Goss, Jeffrey C. Goh, Meiqi Lin, Diana Lim, Jae-Weon Kim, Michael Friedlander, Bee Choo Tai, Kidong Kim, David Shao Peng Tan
Journal: Journal of Clinical Oncology (2023)

e17564 Background: In the phase II MOCCA/ APGOT-OV2/ GCGS-OV3 trial, D was not superior to PCC in prolonging progression-free survival in patients with rOCCC. Fewer all-grade and high-grade adverse events were observed for patients treated with D compared with PCC. We analysed health-related QoL by treatment arm. Methods: In this multicentre, open-label, randomised phase II trial, eligible patients were randomly assigned (2:1), using dynamic block randomization with block size of 6, and stratification by Eastern Cooperative Oncology Group performance status, to receive D (1500mg on day 1, in 28-day cycles) or PCC until disease progression, intolerable toxicity or withdrawal of consent. Patients treated with PCC were able to receive any agent deemed appropriate by the Investigator, however the addition of anti-angiogenic drugs was prohibited. Patients with disease progression on PCC were allowed to crossover to D. Patients completed European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OV28 QoL questionnaires at baseline and every 4 weeks until end of study treatment. The minimal important difference for clinically relevant change was fixed at 10 points. Linear mixed-effects models were used to estimate the treatment effect on QoL outcomes, accounting for the intra-subject correlation in QoL scores at repeated visits from treatment cycles 2 to 6, while adjusting for baseline QoL scores (cycle 1 day 1) and time of visit. We included all patients whose QoL scores were available at both baseline and at least one visit from cycles 2 to 6. Results: 47 patients were randomly assigned to treatment with D (31 patients) or PCC (16 patients). Compliance to QoL questionnaires was 81.6 % (D) and 87.5% (PCC) at baseline. QoL data was available for 22.6-81.6% (D) and 31.3-87.5% (PCC) of patients over time. Longitudinal analysis of QoL data by domain revealed no significant differences in global health status, functional scales or most of the symptom scales based on EORTC QLQ-C30 or QLQ-OV28 between patients treated with D compared with PCC, except for the Constipation symptom scale on QLQ-C30 which showed an estimated mean difference of -20.8 points (95% confidence interval (CI), -31.5 to -10.2; p = 0.001) and the Hair loss symptom scale on QLQ-OV28 which showed an estimated mean difference of -19.6 points (95% CI -36.6 to -2.6; p = 0.025). Conclusions: D and PCC did not lead to significant differences in patient-reported global health status or functional scales. However, PCC was associated with increased patient-reported constipation and hair loss compared with D in rOCCC. Clinical trial information: NCT03405454 .
Can epigenetic treatments efficiently revoke the ability of 3D ovarian cancer cells to proliferate, migrate, and invade?
Authors: Rebeca Kelly, Diego Aviles, David Philip Warshal, Lauren Krill, Olga Ostrovsky
Journal: Journal of Clinical Oncology (2023)

e17562 Background: 3D ovarian cancer propagation and metastasis arise not only from genetic mutations, but from aberrant epigenetic modifications known to involve mechanisms of DNA methylation and histone deacetylation. Clinically, cancer induces epigenetic aberrations in adipose-derived stem cells from omentum (O-ASCs), creating a tumorigenic microenvironment that supports chemoresistance and dissemination of disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we investigate whether these diet-derived compounds can suppress proliferation, migration and invasion of ovarian cancer in 3D-spheroids or 3D-organoids with O-ASCs when compared to synthetic Panobinostat (Pano) and cisplatin/paclitaxol (C/T). Methods: 3D ovarian cancer spheroids and organoids (30% O-ASCs) were treated with EGCG (10, 50 µm), I3C (50, 200 µm), Pano (5, 15 µm) and C/T. Percent growth was followed for 17 days and compared to an untreated control group. Post-treated cancer was then derived from 3D structures and tested for its ability to regrow (MTT assay), to form colonies (CFU), and to migrate and invade (CytoSelect Cell Migration and Invasion assay). Results: Our results show that higher doses of epigenetic regimens more efficiently suppress growth of 3D ovarian cancer when compared to the control and C/T groups (p&lt;.05). Additionally, the synthetic epigenetic drug Pano also efficiently suppressed cancer as compared to control and C/T treated cells (p&lt;.05). Given that experimental treatments efficiently down-regulated 3D cancer growth, follow up of post-treatment cancer recovery was analyzed through multiple biochemical and biological assays. 3D derived cells pre-treated with EGCG, I3C and Pano had significant lower proliferation capacity as compared to control or C/T as demonstrated by an MTT assay (p&lt;.05). While all epigenetic treatments inhibited CFU in the spheroid derived group, EGCG was not able to fully inhibit CFU in the organoid group. Further, inhibition of CFU was not noted in the C/T pre-treated cells. Finally, the ability of cells to migrate and invade following treatment was more efficiently suppressed in cells derived from organoids. I3C and Pano significantly suppressed cancer migration, while EGCG and Pano suppressed invasion (p&lt;.05). Conclusions: Diet-derived epigenetic treatments can reprogram epigenetic aberrations involved in mechanisms of proliferation, migration and invasion of 3D ovarian cancer. Our results suggest that these treatments not only suppress 3D cancer growth and post-treatment regrowth, but could be considered as adjuncts to standard chemotherapy, improving efficiency and patient outcomes.
The Onc Docs: Partnering with Black cancer patients for cancer education.
Authors: Fiyinfolu Balogun, Onyinye Balogun
Journal: Journal of Clinical Oncology (2023)

e18681 Background: In 2022, there will be approximately 224,080 new cancer cases and 73,680 cancer deaths among Black individuals in the United States. Black people are disproportionately burdened by cancer due to higher incidence and mortality levels across multiple cancer types. Yet, their stories are underrepresented in media and the top podcasts for cancer education do not feature Black experts. We formed our podcast, The Onc Docs, to highlight the (under-told) stories of Black individuals with cancer and to provide education about cancer from Black patient survivors, patient advocates and oncologists.We sought to understand the current landscape of podcasts focused on the Black cancer experience &amp; to assess public engagement with The Onc Docs across social media platforms. Methods: We conducted a search of "Black cancer" in Google, Spotify and Apple podcasts. Search engines were also utilized to identify podcasts with a focus on the Black cancer experience. Finally, we reviewed our publicly available listener and follower statistics. Results: At least 12 podcasts on the Black cancer experience were identified with the majority available on Google Podcasts. Seven of the twelve podcasts focused on breast cancer in Black women while two podcasts discussed prostate cancer and one featured brain tumors. Two podcasts (17%) published episodes for one or more years. The remaining podcasts (n = 10) were in existence for an average of 3 months. Three podcasts had published an episode in 2022. Since starting our podcast in September 2020, we have 958 Twitter followers and 400 followers on Instagram. According to Spotify, from 2021-2022, our podcast was heard in 4 countries, increased 87% in streams, 40% in listeners and 235% in hours spent listening to our episodes. On Google Podcasts, we have 4 subscribers. Each month, about 100 unique visitors navigate to our website. Conclusions: Podcasts on the Black cancer experience are needed especially those with a focus apart from breast cancer. Prior podcasts may lack longevity due to a lack of financial and infrastructural support needed to sustain a podcast. In the past year, our work has garnered attention from the general public and gained traction with patient advocacy and scientific associations like Black in Cancer, Cancer Research UK, and Touch Breast Cancer. However, additional efforts &amp; support are needed to ensure consistent creation and delivery of episodes. For instance, we can utilize Facebook, the largest social media platform, to expand our reach. With future growth, we will be able to access data analytic tools to determine the demographic breakdown of our audience and if we are reaching Black listeners.
Melanoma disparities in urban vs rural communities in the era of immunotherapy: An NCDB analysis.
Authors: Rachel Akers, Alison Coogan, Laura Kasper, Vaishnavi Krishnan, Alan Tan, Cristina O'Donoghue
Journal: Journal of Clinical Oncology (2023)

9578 Background: Several barriers to care exist for melanoma patients including distance to specialty care, transportation, and cost. Additionally, differences in rural and urban melanoma incidence have not been fully investigated. Using a large nationwide database, we aim to investigate the relationship between urban and rural locations in stage of melanoma presentation and access to adjuvant systemic treatment. Methods: The National Cancer Database (NCDB) was queried for all adult patients (≥ 18 years old) with diagnosis of cutaneous melanoma from 1/1/2011 – 12/31/2020. For receipt of adjuvant immunotherapy, diagnosis from only 1/1/2017 - 12/31/2020 was analyzed. Demographic, socioeconomic, tumor-related, and treatment-related factors were analyzed using SPSS Statistics, with Chi-square analysis performed for categorical variables and ANOVA performed for continuous. Results: Between 2011 and 2020, 558,445 patient cases were identified and included in the analyses. The average age was 63.7 years, and patients predominantly identified as White (97.6%) and non-Hispanic (96.2%). Patients in urban areas were more likely to present with melanoma of the extremities (40.8% vs 36.2%, p &lt; 0.001), while patients in rural areas presented with head and neck melanoma (26.2% vs 31.0%, p &lt; 0.001). Additionally, patients in urban areas were more likely to have an early-stage melanoma (0, 1, or 2) melanoma (51.4% vs 48.5%, p &lt; 0.001). Patients in rural areas traveled an average of 68 miles for care, in contrast to urban patients who traveled an average of 20 miles (p &lt; 0.001). There was no significant difference when comparing receipt of immunotherapy for stage 3 or stage 4 patients. Conclusions: In rural areas, patients with melanoma tended to present with a higher portion of head and neck melanoma and of later stage. Rural patients also had to travel farther for care. However, these differences did not result in fewer patients in rural areas receiving immunotherapy for appropriate treatment. Further studies are needed to evaluate how these presentation differences influence care outcomes.
The landscape of <i><i>BRCA1</i></i> and <i><i>BRCA2</i></i> alterations in Chinese ovarian cancer patients.
Authors: Minmin Hou, Li Sun, Xiuzhang Yu, Pengyao Du, Chuang Liu, Fanfan Meng, Yaxuan Zhang, Ling Li
Journal: Journal of Clinical Oncology (2023)

e17565 Background: BRCA1 and BRCA2 are tumour suppressor genes, involved in the homologous repair of double-stranded DNA breaks, located at 17q21.31 and 13q13.1, respectively. Germline BRCA1/2 mutations are identified in 13-15% of ovarian cancers (OC), while an additional 5-7% of ovarian cancers harbor somatic BRCA1/2 mutations among foreign populations. To determine the landscape of germline and somatic pathogenic BRCA1 and BRCA2 alterations in Chinese patients with ovarian cancer tested by next‐generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing. Methods: 472 normal-paired samples from Chinese patients with ovarian cancers were analyzed using hybridization capture-based next generation sequencing. Somatic and germline mutations were identified including 500 genes associated with tumor development. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (InDels), copy number alterations (CNA) and gene fusions and rearrangements. Results: Overall, 472 ovarian cancer patients underwent somatic and/or germline NGS analysis, the BRCA1 and BRCA2 genes sequenced in this study covers all targeted coding exons and exon-intron boundaries. Among these patients, 54/472 (11.4%) patients carried BRCA( BRCA1/2) mutations. Inside, there were 43/472 (9.1%) patients occurred somatic BRCA mutations, 62.8% (27/43) of variants were in BRCA1 and 37.2% (16/43) were in BRCA2. Furthermore, 3 cases carried BRCA1 and BRCA2 somatic co-mutation, of which only 1 showed BRCA1/ BRCA2 copy number losses. In 54 OC patients who carried BRCA mutations, 10 patients occured copy number alterations, of which 6 patients showed BRCA1 copy number losses, 4 patients showed BRCA2 copy number losses, and 1 patient showed BRCA2 copy number gains. Germline BRCA variant was detected in 18/472 (3.8%) patients, 66.7% (12/18) of variants were in BRCA1 and 33.3% (6/18) were in BRCA2. Of the 12 BRCA1 germline mutations, 11 were pathogenic heterozygous mutations (c.2679_2682del; c.2101_2102del; c.5085_5086insT; c.1660G &gt; T; c.4810C &gt; T; c.1504_1508del; c.1465G &gt; T; c.1480C &gt; T; c.2110_2111del; c.4185+1G &gt; A; c.81-2A &gt; G), one was likely pathogenic heterozygous mutation (c.5216A &gt; G). Of the 6 BRCA 2 germline mutations, four were pathogenic heterozygous mutations (c.5722_5723del; c.5291C &gt; G; c.5164_5165del; c.3109C &gt; T), one was likely pathogenic heterozygous mutation (c.869_870del), and one was uncertain significance heterozygous mutation (c.7976+3A &gt; G). Conclusions: This study revealed the molecular features of BRCA1 and BRCA2 in Chinese ovarian cancer patients, which could help to identify therapeutic targets and personalize therapy management, leading to improved patient outcomes as predictive biomarkers or platinum-based therapy.
Postoperative prognosis in patients with NSCLC with different EGFR mutation sites.
Authors: Chao Dong, Hushan Zhang, Weiqing Liu, Deyu Kong, Xiao Chen, Fei Mo, Jun Deng, Ying Qian
Journal: Journal of Clinical Oncology (2023)

e20528 Background: Lung cancer can be divided into small cell lung cancer and non-small cell lung cancer. At the same time, non-small cell lung cancer can be divided into non-small cell lung cancer with different molecular mutations. Among them, the EGFR mutation accounts for about 50% of the patients with non-small cell lung cancer in China, which is a large group of patients. The EGFR mutation has many sites and many forms of mutational subtypes, including common mutations such as L858R, and rare mutations. Although the proportion of rare mutations is small, it is still different from common mutations in patients with TKI treatment and immunity. Methods: This study collected and analyzed the data from Formalin-Fixed Paraffin-Embedded (FFPE) tissues of 330 NSCLC patients which received surgery and underwent a targeted next-generation sequencing (NGS) assay performed by 3DMed Clinical Laboratory Inc., a College of American Pathologists (CAP) certified and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory of 3D Medicines Inc. between January, 2019 and June, 2022 in China, to obtain a comprehensive molecular profile of EGFR mutations. genomic alterations, tumor mutational burden (TMB) and PD-L1 expression were analyzed. Gene mutation and TMB level were analyzed by NGS, detected PD-L1 expression by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. Finally, the postoperative follow-up data were also collected and analyzed in this study. Results: Therefore, we retrospectively analyzed the tissue samples of patients with non-small cell lung cancer who received surgical treatment, and carried out NGS detection and analysis, as well as postoperative follow-up. Among them, patients with EGFR mutations accounted for 51.2%. We further analyzed the TMB and PD-L1 expression levels of different EGFR mutation subtypes. First, we found that different EGFR mutation sites, whether common mutations such as L859R, 19del or unusual mutations such as S768I, There is no difference in the prognosis after operation, but it is very significant that our results show that there are two or more EGFR mutations at the same time. Conclusions: NSCLC with EGFR mutation is a very large group of patients, which should be further subdivided into different subtypes according to different EGFR mutation sites, and should perform individualized management. This study found that patients with two or more EGFR mutations and patients with EGFR single site mutations are different types of NSCLC, with different postoperative prognosis, and it may be related to the differences in the expression levels of TMB and PD-L1, which is a direction worthy of further exploration in the future.
A robust and accurate method to detect MET Exon 14–skipping mutation in pan-cancer samples using an NGS-based RNAseq approach.
Authors: Yongjie Wang, Ren HengDa, Yiqun Zhang, Zhihua Pei, Dongliang Wang, Qiming Zhou, Jing Wang
Journal: Journal of Clinical Oncology (2023)

e20575 Background: Met exon 14 skipping mutation(METex14) occurs in multiple cancer species, mainly in non-small cell lung cancer (NSCLC, 3~4%) and pulmonary sarcomatoid carcinoma (PSC, 22%). Several drugs expressed curative effect in previously treated patients who harboring METex14, such as savolitinib approved by NMPA, capmatinib and tepotinib licenced by FDA. Developing a quick and precise method which detect METex14 and help patients benefit from clinical drug treatment is a desiderative issue currently. Previous researches suggest that transcriptome-based RNA-seq method was superior to DNA-based NGS (exome, panel) and PCR method. Here We introduce a fast and accurate method to detect METex14 alternation in RNAseq data. Methods: We sequenced NGS-based Ribo-zero RNAseq (pair-end, 150bp×2) and METex14 ddPCR on 99 pan-cancer samples, of which 38 lung carcinoma (38%), 8 renal carcinoma (8%), 7 pancreatic carcinoma (7%). In 38 lung carcinoma, 35 NSCLC samples were consist by 29 lung adenocarcinoma (LUAD, 76%), 4 lung squamous carcinoma (LUSC, 10%) and 2 PSC (5%). Begin of the study, data quality control applied by Fastp and aligned to human hg19 genome by STAR subsequently. Next, MET exon14 related candidate soft-clipping reads were extracted from BAM files and translated to fastq file. Then we remapped the translated fastq file to hg19 genome with Blat using parameters ‘stepSize = 5, -repMatch = 2253, -minScore = 20, -minIdentity = 90’. Next, supporting reads were sequentially retained by: single end length longer than 18bp; block mapped reads of MET gene; the pair end reads mapped to genome if one end fall in the last 3bp of MET intron 13 and another end fall in at least initial 3bp of MET exon 15. Pair or single end support junction read, distance of junction site to reads end and site coverage were enrolled in a bayesian model to calculate METex14 confidence score (BMMETs). Threshold of our model was defined by the cut-point of max youden-index and 16 samples were validated METex14 by ddPCR. Finally, we would predict a sample with METex14 when score &gt; = 0.752. Results: Our method reported 15 TP samples, 1 FP sample and 1 FN samples (AUC 0.97, sensitivity 0.88, specificity 0.98) while STAR-fusion detected 14 TR samples and 6 FP sample and 2 FN samples (AUC 0.715, sensitivity 0.64, specificity 0.73). BMMETs FP sample scored approximately 0.739 that close to the threshold. Conclusions: Strategy of screen reliable METex14 supporting reads and using bayesian model to calculate a METex14 confidence score could robustly and efficiently predict METex14 event in NGS-based RNAseq data.
The mortality burden of cachexia in patients with non-small cell lung cancer: A meta-analysis.
Authors: Philip D. Bonomi, Jeffrey Crawford, Richard Francis Dunne, Eric J. Roeland, Karen E. Smoyer, Mohd K. Siddiqui, Thomas D. McRae, Michelle I. Rossulek, James H. Revkin, Lisa C. Tarasenko
Journal: Journal of Clinical Oncology (2023)

e24075 Background: Cachexia and weight loss have been linked to poor outcomes in patients with cancer. This study’s aim was to conduct a meta-analysis to estimate the risk of mortality associated with cachexia in patients with non-small cell lung cancer (NSCLC) in studies identified through a systematic literature review (SLR). Methods: A feasibility assessment was undertaken to determine the suitability of conducting a meta-analysis evaluating the impact of cachexia, defined per International Consensus criteria (ICC) or previous weight loss (WL) ≥5% (without specifying a 6-month duration), on overall survival (OS) in patients with NSCLC. The meta-analysis was conducted using a random-effects model, considering variability across studies, and using the identified studies as base case. The impact of heterogeneity was evaluated through sensitivity and subgroup analyses. Standard measures of statistical heterogeneity were calculated for each meta-analysis. Results: Of the 40 NSCLC publications identified in the SLR, 20 (50%) used the ICC definition or reported WL ≥5%. Sixteen studies (80%, n = 6,225 patients, published in 2016 to 2021) met the criteria for inclusion in the meta-analysis: 11 (69%) studies per ICC and 5 (31%) studies per WL ≥5%. Combined criteria (ICC or WL ≥5%) were associated with 82% higher mortality risk versus no cachexia or WL &lt; 5% (pooled hazard ratio [95% CI]: 1.82 [1.47, 2.25]). A subgroup analysis of studies using the ICC definition (hazard ratio [95% CI]: 2.26 [1.80, 2.83]) or WL ≥5% (hazard ratio [95% CI]: 1.28 [1.12, 1.46]) showed consistent findings. Although high statistical heterogeneity (I-square = 88%) was observed across studies, this variability could be disregarded because effect estimates (hazard ratios) from included studies were directionally aligned with considerable overlap in CIs of individual studies. A meta-influence analysis did not identify any potential outliers. Results of the sensitivity and subgroup analyses were consistent with the base case analysis. Cumulative meta-analyses by publication year or data collection midpoint identified no time-varying effect, indicating results were robust to the differing timeframes of publication or data collection. No substantial publication bias, measured via funnel plot analysis, was identified in the meta-analysis. Conclusions: Based on thorough methodologic, clinical, and statistical heterogeneity assessments, the meta-analysis results are robust. ICC-defined cachexia or WL ≥5% were associated with inferior OS in patients with NSCLC. Identifying cachexia or WL ≥5% has important implications for prognosis and treatment of NSCLC.